A study of the metabolism of the branched-chain amino acids has revealed a pathway of catabolism of leucine in which the first step is catalyzed by leucine 2,3-aminomutase. The enzyme, found in bacteria, plants, yeast, and man, is dependent upon adenosylcobalamin and is stimulated by FAD, coenzyme A, NAD, and pyridoxal phosphate. The relation between enzyme activity and various disease states will be examined.